biostudies-literatureLi CNatural Science Foundation of Shandong ProvinceNCI NIH HHS628-639https://www.ebi.ac.uk/biostudies/studies/S-EPMC6644699biostudies-literatureUnknown79(6)<h4>Background</h4>Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells.<h4>Methods</h4>To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis.<h4>Results</h4>Among 14 verified protein targets, four were Krebs cycle enzymes, fumThe ProstateAlternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.PMC6644699ZR2016HL25R01 CA173292He CLi CKrishnamurthy PChavan HHolzbeierlein JMXu HHan SForrest MLDuan SArtigues ALi BTang YXu YfalseAlternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.<h4>Background</h4>Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells.<h4>Methods</h4>To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis.<h4>Results</h4>Among 14 verified protein targets, four were Krebs cycle enzymes, fum2019-01-01T00:00:00Z2019 May2026-05-04T23:37:41.279Z2020-10-29T14:04:58ZS-EPMC66446993066308410.1002/pros.23767